There is overwhelming evidence that low dose methotrexate therapy for psoriasis is effective. However, methotrexate toxicity is a factor which reduces the usefulness of the drug. Since methotrexate is an antimetabolite of the B vitamin, folic acid, folic acid supplements may in theory reduce methotrexate toxicity. It has been previously reported that methotrexate toxicity in rheumatoid arthritis patients is reduced by folic acid supplementation while efficacy of methotrexate in treating the joint disease is preserved. Little is known concerning the mechanism of action of low dose methotrexate in controlling psoriasis. It has been hypothesized that methotrexate suppresses the immune system and as a result reduces the disease activity of psoriasis and other autoimmune diseases (i.e. rheumatoid arthritis). It is known that methotrexate interferes with purine nucleotide metabolism which has the potential of producing immunosuppression substances. The specific aims of this proposal are to demonstrate that a folic acid supplement (7 mg or 38.5 mg/week) will reduce methotrexate toxicity in patients with psoriasis while preserving the efficacy of the drug. A second specific aim is to demonstrate that urinary levels of aminoimidazole carboxamide (AIDA), adenosine (Ado), and deoxyadenosine (dAdo) are elevated in methotrexate-treated patients with psoriasis compared to controls. AICA, Ado, and dAdo are known to be immunotoxic substances and they may be the link between methotrexate therapy, immunosuppression and efficacy in psoriasis therapy. Clinical evaluations of psoriasis disease activity and a toxicity score previously validated in low dose methotrexate-treated rheumatoid arthritis patients, will be used to score both disease activity and drug toxicity. Colorimetric and HPLC determinations of AICA, Ado and dAdo will be employed. It is expected that folic acid supplementation will reduce methotrexate toxicity without altering efficacy. It is expected that AICA, Ado, and dAdo will be elevated in psoriasis patients responding to methotrexate.